Piperaquine

Piperaquine is a synthetic antimalarial drug belonging to the 4-aminoquinoline class. It is primarily used in fixed-dose combination with dihydroartemisinin (DHA-PPQ) for the treatment of uncomplicated malaria caused by Plasmodium falciparum, and sometimes P. vivax. Piperaquine has a long elimination half-life, which offers post-treatment prophylaxis but can contribute to resistance if used alone.

In most settings it is given as the fixed-dose DHA-piperaquine formulation, usually taken orally once daily for three days. The regimen combines the rapid parasite clearance of dihydroartemisinin with the longer-acting piperaquine, helping prevent recrudescence. Dosing is weight-based, with tablets containing both components.

Mechanism: Piperaquine disrupts heme detoxification in the parasite’s digestive vacuole, a mechanism shared with other 4-aminoquinolines. It mainly targets blood-stage parasites. Pharmacokinetics: Piperaquine has a long half-life, is lipophilic, and is primarily cleared via hepatic metabolism and fecal excretion.

Resistance and safety: Reduced susceptibility to piperaquine has emerged in parts of Southeast Asia, often with plasmepsin II/III gene amplifications and other genomic changes in the parasite. Adverse effects include gastrointestinal symptoms and, importantly, QT interval prolongation, which can cause arrhythmias, especially with co-administered QT-prolonging drugs.

History and use: Developed in the late 20th century, piperaquine is widely used in ACT regimens recommended by the World Health Organization for uncomplicated malaria. It is generally not used alone due to resistance, and surveillance monitors efficacy and resistance patterns worldwide.